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KMID : 0383820080650030177
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Tuberculosis and Respiratory Diseases
2008 Volume.65 No. 3 p.177 ~ p.182
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Standard Chemotherapy with Excluding Isoniazid in a Murine Model of Tuberculosis
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Shim Tae-Sun
Lee Eun-Gae
Choi Chang-Min
Hong Sang-Bum
Oh Yeon-Mok
Lim Chae-Man
Lee Sang-Do
Koh Youn-Suck
Kim Woo-Sung
Kim Dong-Soon
Cho Sang-Nae
Kim Won-Dong
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Abstract
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Background: Isoniazid (INH, H) is a key drug of the standard first-line regimen for the treatment of tuberculosis
(TB), yet some reports have suggested that treatment efficacy was maintained even though INH was omitted from
the treatment regimen.
Methods: One hundred forty C57BL/6 mice were infected with the H37Rv strain of M. tuberculosis with using
a Glas-Col aerosol generation device, and this resulted in depositing about 100 bacilli in the lung. Four weeks
after infection, anti-TB treatment was initiated with varying regimens for 4-8 weeks; Group 1: no treatment (control),
Group 2 (4HREZ): 4 weeks of INH, rifampicin (R), pyrazinamide (Z) and ethambutol (E), Group 3: 1HREZ/3REZ,
Group 4: 4REZ, Group 5: 4HREZ/4HRE, Group 6: 1HREZ/3REZ/4RE, and Group 7: 4REZ/4RE. The lungs and
spleens were harvested at several time points until 28 weeks after infection, and the colony-forming unit (CFU)
counts were determined.
Results: The CFU counts increased steadily after infection in the control group. In the 4-week treatment groups
(Group 2-4), even though the culture was negative at treatment completion, the bacilli grew again at the 12-week
and 20-week time points after completion of treatment. In the 8-week treatment groups (Groups 5-7), the bacilli
did not grow in the lung at 4 weeks after treatment initiation and thereafter. In the spleens of Group 7 in which
INH was omitted from the treatment regimen, the culture was negative at 4-weeks after treatment initiation and
thereafter. However, in Groups 5 and 6 in which INH was taken continuously or intermittently, the bacilli grew
in the spleen at some time points after completion of treatment.
Conclusion: TThe exclusion of INH from the standard first-line regimen did not affect the treatment outcome in
a murine model of TB in the early stage of disease. Further studies using a murine model of chronic TB are
necessary to clarify the role of INH in the standard first-line regimen for treating TB.
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KEYWORD
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Tuberculosis, Isoniazid, Mouse
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